Tryptophan hydroxylase gene and major psychoses

Disturbances of the serotoninergic neurotransmitter system have been implic ated in the pathogenesis of mood disorders. The tryptophan hydroxylase (TPH ) gene, which codes for the rate-limiting enzyme of serotonin biosynthesis, has been recently reported to be associated with bipolar disorder. In this study, we investigated TPH A218C gene variants in a sample of subjects aff ected by major psychoses. One thousand four hundred and twenty-four inpatie nts affected by bipolar (n = 627), major depressive (n = 511), schizophreni c (n = 210), delusional (n = 48) disorder and psychotic disorder not otherw ise specified (n = 27) (DSM-IV) were included; all patients and 380 control s were typed for the TPH variants using PCR techniques. A sub-sample of 963 patients was assessed using the Operational Criteria for Psychotic Illness (OPCRIT). TPH variants were not associated with major psychoses, but a tre nd was observed toward an excess of TPH*A/A in bipolar disorder. The analys is of symptomatology factors did not show any significant difference either ; however, a trend was observed for males with the TPH*A genotype to have l ower depressive symptoms compared with TPH*C subjects. Possible stratificat ion factors such as current age and age of onset did not affect the observe d results. TPH A218C variants are not, therefore, a major liability factor for the symptoms of major psychoses to have in the present sample, TPH*A co ntaining variants may be a protective factor for depressive symptoms among male subjects with mood disorders or for a subtype of mood disorders charac terized by a mainly manic form of symptomatology. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.